The analysis of a large number of human and mouse solid tumors has established the relevance of genomic imbalances as the premier genetic aberration in cancers of epithelial origin. 95% of all aberrations result in copy number changes reflecting gains and losses of specific chromosomes, chromosome arms and chromosomal regions. Therefore, solid tumors differ in their cytogenetic aberration pattern from hematological malignancies, that are characterized by chromosomal translocations of which about 50% are balanced, reciprocal ones. The dominance of chromosomal gains and losses, in particular at early stages during carcinogenesis, suggests that an impairment of chromosome segregation fidelity plays a central role in the genesis of epithelial cancers. Based on this observation we have identified the following problems:* are there abnormalities of cellular structures that regulate chromosome segregation thereby causing the emergence of chromosomal aneuploidy and what role does the centrosome, as the major organizer of the spindle apparatus, have in the proper segregation of chromosomes* is there a karyotypic difference between diploid and aneuploid tumors, and can aberrations in centrosome number and function lead to chromosomal aneuploidy in human and mouse tumors To address these problems we propose to:* develop live cell imaging in combination with the use of green fluorescent protein technology to explore the sequence of chromosomal copy number changes and centrosome aberrations* develop model systems to study the effects of extra copies of specific chromosomes in normal cells - chromosomes, mitosis, centrosomes, - Neither Human Subjects nor Human Tissues